Despite the prevalence of mosquito-transmitted diseases such as malaria and dengue, little progress has been made in the development of a safe mosquito repellent. In the middle of last century a large number of compounds were evaluated in-vivo for repellency against Aedes aegypti(the yellow fever mosquito) and other species of blood-sucking mosquitoes. The study was a large random search through a variety of chemical structures, most of them organic, which provided several potential compounds for development. From these studies, the most popular mosquito repellent today, N,N-diethyl-m-toluamide (DEET, or m-DEET), emerged first for the use of the US Army and later for use of the general public. A few animal studies on DEET have shown a range of toxic effects ranging from skin irritation to adverse neurological effects. Other compounds, natural and synthetic, have been used but due to their range of action and level of safety have had little success compared to DEET.
The development of safe repellents has been hampered by the poor knowledge of the mosquito's receptors and the difficulties involved in the testing of new substances. In addition to the lack of molecular targets (receptors) for rational design, the testing of new chemicals as potential repellents using humans is variable and intrinsically dangerous, since the toxicology of the new substance is usually not known. The in-vivo test in practice today dates back to 1919 and uses the forearm or the hand of human subjects exposed at short time intervals to hungry mosquitoes. Other methods have been tried in order to overcome the shortcomings of the human test but none have prevailed due to the fact that most of them rely on the attractants of an animal subject and the need of a hungry female mosquito. Reliability of the human test is questionable. Early verification of the activity of DEET, for instance, gave zero activity in the first test using the arm, lasted 2 h in a Russian measurement using the forearm, and 5 h using a hand test. Number and degree of hunger of the mosquitoes, concentration of the repellent, and differences in the type of attractants released by the human subjects can account for the discrepancies. Furthermore, because the method is based on the attractants released on the skin, the human test cannot distinguish between substances that actually affect the sensory system of the insect (true repellents) and those that block the release of those attractants from the skin (attractant blockers).
There is therefore a need to develop a better testing method for the evaluation of mosquito repellents such as the one described here. This new approach overcomes the limitations of the human method by not relying on the attractants present in the human skin or on the need of the female mosquito of a blood meal. Thus, this method differentiates between true repellents and attractant blockers. This method is based on the disturbance created by the repellent of the natural tendency of the mosquito to rest in certain rough surfaces above ground.